New COVID-19 variants have ‘major impact’ on prevention for cancer cell therapy recipients
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The FDA recently withdrew its emergency use authorization for Evusheld, a combination monoclonal antibody therapy used to prevent COVID-19 among high-risk individuals.
The agency revised guidance on emergency use of Evusheld (tixagevimab plus cilgavimab, AstraZeneca) to when the combined national frequency of variants not susceptible to the treatment is 90% or less.
“This means that Evusheld is not expected to provide protection against developing COVID-19 if exposed to those variants,” the statement added. “[This] action to limit the use of Evusheld prevents exposing patients to possible side effects of Evusheld, such as allergic reactions — which can be potentially serious — at a time when fewer than 10% of circulating variants in the U.S. causing infection are susceptible to the product.”
The FDA withdrawal was necessary because of the emergence of the XBB1 strain as the dominant strain of COVID-19 in circulation, according to Genovefa Papanicolaou, MD, attending physician and infectious diseases specialist at Memorial Sloan Kettering Cancer Center.
“From as early as October, there were concerns that Evusheld may lose activity if XBB1 became the dominant strain,” Papanicolaou told Healio. “Right now, this variant represents 90% of the infections in the U.S.”
Patients with blood cancers who undergo cellular therapy — including chimeric antigen receptor T-cell therapy and hematopoietic stem cell transplant — are more susceptible to COVID-19 infection.
Add to this a level of uncertainty about the effectiveness of vaccines in this population, and COVID-19 prevention measures have become standard for all cell therapy/transplant centers and recommended by the CDC, ASH and American Society for Transplantation and Cellular Therapy.
The FDA’s withdrawal of the emergency use authorization for Evusheld was medically appropriate, but the lack of availability is of secondary concern for CAR-T/HSCT providers, according to David L. Porter, MD, director of cell therapy and transplantation at University of Pennsylvania’s Abramson Cancer Center and a member of the Healio | Cell Therapy Next Peer Perspective Board.
"The major issue is that there is no longer an intervention that will likely provide meaningful protection for those patients who can’t mount an immune response to vaccines and are at high risk for complications from COVID,” Porter told Healio. “Novel variants will have a potential major impact on cell therapy and HSCT recipients.”
Sanjeet Dadwal, MD, is chief of the division of infectious diseases at City of Hope, one of many HSCT/CAR-T providers that recommended patients undergoing either therapy take Evusheld as COVID-19 prophylaxis either at admission before the treatment or upon discharge.
It was just a matter of time before variants emerged for which Evusheld would be ineffective — much the way it had for previous monoclonal antibodies, he said.
“The FDA announcement came as no surprise,” Dadwal told Healio. “There was mounting evidence that newer strains would not be susceptible to [Evusheld].”
Dadwal agreed with Porter and confirmed there are no available therapies for COVID-19 prophylaxis due to the FDA’s withdrawal of Evusheld’s emergency use authorization.
“Even when we provided these monoclonal antibodies to patients, we would always give the same recommendation [to] be careful because their immune system is compromised and they may not work,” Dadwal said.
Physicians in the transplant/cell therapy space were aware of the waning effectiveness of Evusheld, Papanicolaou said.
“Prevalence of XBB1 from 0 to 90% did not occur instantly — it was a gradual increase,” she said. “But we had not altered our practice of giving [Evusheld] until the FDA pulled its emergency use authorization.”
Cell therapy and transplant centers are being told to hold on to their supplies in case subsequent variants are susceptible to the antibodies in Evusheld, Papanicolaou said.
Such a back and forth between effectiveness and ineffectiveness would not be unprecedented based on the history of the disease, she added.
Despite the lack of a medically based COVID-19 prophylaxis option, the balance of most COVID-19 prevention advice remains intact. These include masking in public, avoiding crowds when possible and washing hands, in addition to receiving a full vaccination and bivalent booster series, Dadwal said.
Effective treatment options remain to lessen the severity of COVID-19 among cell therapy recipients, he added. Clinicians should remind their patients to inform the care team immediately in these cases.
Nirmatrelvir/ritonavir (Paxlovid, Pfizer), remdesivir (Veklury, Gilead Sciences) or molnupiravir (Lagevrio, Merck) have all been approved under an FDA emergency use authorization for post-exposure use and remain effective against current variants, Dadwal said.
(Editor’s note: FDA approved remdesivir on October 22, 2020, for use in adult and pediatric patients 12 years of age and older and weighing at least 40 kg for the treatment of COVID-19 requiring hospitalization. The emergency use authorization issued on May 1, 2020, includes use for treatment of suspected or laboratory confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg.)
For more information:
Sanjeet Dadwal, MD, can be reached at sdadwal@coh.org.
Genovefa Papanicolaou, MD, can be reached at papanicg@mskcc.org.
David L. Porter, MD, can be reached at david.porter@uphs.upenn.edu.
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